Methylene-disalicylic-acid derivative



Patented 1...... 17, 1930 1,764,036 I I I a I i i UNITED STATES PATENTOFFICE SAMUEL LEWIS SUMMERS,,OF FORT WASHINGTON, PENNSYLVANIA i iMETHYLENE-DISALICYLIC-AGIID DERIVATITTE No Drawing. Application filedJuly 5, 1928. Serial No. 290,710.

My invention relates to organic com- The next main step is acondensation treat- I pounds and their manufacture, and is espement ofthis amide with benzaldehyde, which cially' concerned with a novelcondensation may be performed as follows: product ofmethylene-diethyl-salicylate (and Mix and heat 348 pounds of this amideits homologues hereinafter indicated) with (prepared as above described,or in any other benzaldehyde and pyruvic acid. My new suitable Way)under a reflux condenser with products are useful for pharmaceuticalpur- 212 pounds of benzaldehyde and a condensing poses, as hereinafterset forth, agent (say 212 pounds of zinc chloride), and

My product may be prepared as follows:- also 522 pounds of ethylalcohol,'-these pro- Starting with Inethylene-disalicylic acid, portionsbeing by weight,maintaining a the first step is esterificat-ion. Varioustemperature of about'80 C. for 48 hours. homologous esters may beproduced in the The essential product appears to be a methyl- I mannerhereinafter described,by using ene dibenzal disalicyl compound, correthecorresponding methyl, ethyl, propyl or sponding to the empirical formulal; other a1cohols,-with a corresponding difi'era CMHMO N9 ence in theesterification product. A Way of 4 ""carrying out the est rificati ithth l 1. I believe the reaction and the structural for- 1 1 i as f ll.mula of the product to be as follows:

Dissolve 288 lbs. of methylene-disalicylic on :0 acid in 150 lbs. ofethyl alcohol, and slow- 65 ly add to the solution, at a temperature ofH 70 0., a solution of 60 lbs. 66 B. sulphuric y +010 acid diluted with40 lbs. water. lVhen this has all been added, raise the temperature to:3 C. under a reflux condenser, and hold CH CON:CH.Cu 5 70 at thistemperature for about 2 hours. The 1 on eis septilal 1prolditict is theester, methylene- (let -sa1c aez' y y l The next main step is acondensation treatn .ment of this product (the methylene-difl 3( QCaH5benzal-di salicyl compound) with pyruvic This may be Washed free of anysulphuric acldzwhlch m y be Performed as follows: a id l ft Over f th eti Mix the sald product, obtained as above lhe next 1113111 tep isconvert ester described, \Vltll OT pyruvic acid, and 35 to an amide,which may be done as follows: h t 1300 0'? mamtammg h p Dissolve theester in 120 of 6 f ature for 24 hours. The essentlal product aqueousammonia (u na 28% (difficult to name) appears to correspond to NH andheat the solution under pressure fl w g D and I (in' an autoclave),maintaining it at a tem- Its i ma Ormu to perature of 110 C. for eighthours. The es-, Cu K000000111 S5 sential product ismethylene-chsalicyl-amide, CH2 CON 3 5 having the formula: (a ooooooin ZC0H:(OH)CONH2 CONICHColTfi CaEMOHKJONHa It is a crystalline substance,insoluble in 90 cold wa teiy but soluble in alcohol. It has valuablepharmaceutical properties and uses, partlcularly as an antiseptic,

antineuralgic, antiarthritic, and antirheumatic. Dosage (internal1y),'90to 180. grains per day.

Having thus described my invention, I claim:

The hereindescribed condensation product of methylene-disalicyl-amidesuccessively with benzaldehyde and pyruvic acid; insolfible in coldwater, but soluble in alcohol.

In testimony whereof, I have hereunto signed lnyname at Philadelphia,Pennsylvania; this 29th day of J une,,1928. SAMUEL LEWIS SUMMERS.

